Meng Tingting, Gao Ting, Qiao Fangxia, Xu Hongxia, Yu Na, Zuo Wenbao, Yang Jianhong
Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia, China; Department of Pharmaceutical Preparation, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia, China.
Int Immunopharmacol. 2025 Feb 6;147:114033. doi: 10.1016/j.intimp.2025.114033. Epub 2025 Jan 11.
Herpes zoster is an acute infectious skin disease caused by the reactivation of latent varicella-zoster virus, vaccination, such as subunit vaccine with good safety, can effectively prevent shingles through increasing immunity of the body. However, protein antigens are prone to degradation and inactivation, which alone is generally not sufficient to induce potent immune effect. In this study, the liposomal vaccine platform modified with mPLA (TLR4 agonist) was developed to improve the immunogenicity of glycoprotein E (VZV-gE) derived from herpes zoster virus. The thin-film dispersion and freeze-drying methods were employed to encapsulate VZV-gE against degradation, enhance liposomal stability, and achieve better redissolution effects with an optimized cryoprotectant. The in vitro results presented that mPLA could effectively enhance the uptake of VZV-gE with DC2.4. In vivo immune effect evaluation showed that the prepared subunit vaccines could induce stronger IgG, IgG1, and IgG2a antibody levels in the mouse serum, improving humoral immune effects. And the secretion levels of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4, IL-10) in the splenocytes were significantly increased, inducing protective cellular immune responses. Overall, this work presented that combining immunomodulatory adjuvants decorated nanocarriers to develop subunit vaccine platforms was a promising strategy to prevent the occurrence of herpes zoster effectively.
带状疱疹是由潜伏的水痘-带状疱疹病毒重新激活引起的一种急性传染性皮肤病，接种疫苗，如安全性良好的亚单位疫苗，可通过增强机体免疫力有效预防带状疱疹。然而，蛋白质抗原容易降解和失活，单独使用通常不足以诱导强大的免疫效果。在本研究中，开发了用mPLA（TLR4激动剂）修饰的脂质体疫苗平台，以提高源自带状疱疹病毒的糖蛋白E（VZV-gE）的免疫原性。采用薄膜分散法和冷冻干燥法包封VZV-gE以防止其降解，增强脂质体稳定性，并通过优化的冷冻保护剂实现更好的再溶解效果。体外结果表明，mPLA可有效增强DC2.4对VZV-gE的摄取。体内免疫效果评估表明，制备的亚单位疫苗可诱导小鼠血清中更强的IgG、IgG1和IgG2a抗体水平，改善体液免疫效果。并且脾细胞中Th1细胞因子（IFN-γ、IL-2）和Th2细胞因子（IL-4、IL-10）的分泌水平显著增加，诱导保护性细胞免疫反应。总体而言，这项工作表明，结合免疫调节佐剂修饰的纳米载体来开发亚单位疫苗平台是有效预防带状疱疹发生的一种有前景的策略。
